ABSTRACT
Robust methodology to install amide, carbamate, urea and sulfonamide functionality to the 1,8-naphthalimide scaffold has been developed and exemplified. New benzamidonaphthalimide 6, synthesised using this approach, was found to be sensitive to base whereupon fluorescence emission strongly increases (>10-fold) and red-shifts (>4000 cm-1). The optical properties of deprotonated 6 allow for single molecule fluorescence detection, the first example of such behaviour from this class of fluorophore.
ABSTRACT
Polynorbornenes substituted with two different peptide sequences from the RGD-containing integrin cell-binding domain of fibronectin are potent inhibitors of human foreskin fibroblast cell adhesion to fibronectin-coated surfaces. Ring-opening metathesis polymerization (ROMP) using Ru==CHPh(Cl)(2)(PCy(3))(DHIMes) (1) as an initiator produced polymers substituted with GRGDS and PHSRN peptide sequences. The inhibitory activity was quantified for these polymers and compared to the free peptides and GRGES-containing controls. A homopolymer substituted with GRGDS peptides was significantly more active than the free GRGDS peptide (IC(50) of 0.18 +/- 0.03 and 1.33 +/- 0.20 mM respectively), and the copolymer containing both GRGDS and PHSRN is the most potent inhibitor (IC(50) of 0.04 +/- 0.01 mM). These results demonstrate that significant enhancements of observed biological activity can be obtained from polymeric materials containing more than one type of multivalent ligand and that ROMP is a useful method to synthesize such well-defined copolymers.
Subject(s)
Cell Adhesion/drug effects , Fibronectins/metabolism , Oligopeptides/pharmacology , Plastics/pharmacology , Cell Line , Fibroblasts/drug effects , Fibroblasts/metabolism , Humans , Magnetic Resonance Spectroscopy , Models, Chemical , PolymersABSTRACT
We report on several pediatric patients in whom multiple surgical procedures were performed under the same anesthesia. The hospital cost is compared with the estimated cost if the procedures were performed separately. The savings were considerable, and there was no increase in morbidity and no lessening of the quality of results.
